North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TXDepartment of Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, TX

Recently mice have been extensively used as an experimental model for glaucoma. The mouse eye bears many similarities to the human in terms of anatomy, physiology, and pharmacology. However, its small size presents a challenge for the study of aqueous humor dynamics (AHD). Mouse AHD parameters have been studied by several laboratories in various strains, but there is no clear consensus. We hypothesize that strain differences may play a role. This study was designed to evaluate potential differences in AHD among several commonly used mouse strains with or without ocular hypertension induced by intraocular injection of a viral vector encoding mutant myocilin.

Intravitreal injection of Ad5.MYOC.Y437H significantly increased IOP in BALB/cJ mice (P<0.001), A/J mice (P=0.001) and C57-BL/6J mice (P<0.001). Mean C in A/J mouse eyes was greater than that of BALB/cJ mouse eyes (1.24× (naïve); 1.21× (injected)), and mean C in C57-BL/6J mouse eyes was greater than that of BALB/cJ mouse eyes (1.52× (naïve); 1.26× (injected)). In each strain, C in eyes injected with Ad5.MYOC.Y437H was significantly reduced, by a factor of 1.32× (BALB/cJ), 1.35× (A/J) and 1.58× (C57-BL/6J) compared with uninjected contralateral eyes (P=0.00716, ANOVA). Fu and Pe were not found to be significantly different between the BALB/cJ and the A/J strains, nor between the naïve or Ad5.MYOC.Y437H-injected eyes within these strains.

Conclusions

There are strain differences in C but not in other AHD parameters. Intravitreal injection of a vector encoding mutant myocilin increased IOP mainly due to a reduction in C.